For many years it has been well known that injection of antigen into animals leads to the activation and proliferation of CD4 bearing T cells. Once the activated T cells have clonally expanded to a maximal level, the majority of them go on to die via apoptosis. This event raises the problem of how antigen-primed T cells ever survive long enough to develop into memory cells. Thus many of these T cells must be able to resist death otherwise a memory response directed towards the antigen would never occur. Recently, it has been shown that T cell clonal expansion in the face of an inflammatory response prevents the death of activated T cells. Therefore, T cells that respond to antigen at an inflammatory site will be spared from activation-induced death. It has been proposed that the activated T cells receive a survival signal which deregulates the death program. For example, co-injection of an antigen with the pro-inflammatory bacterial byproduct, lipopolysaccharide (LPS), leads to long-term T cell survival of the antigen responsive cells. Furthermore, LPS injection conditions these cells to resist FAS-based death. The nature of the T cell survival signal is unknown. The experiments in this project are designed to uncover the underpinnings of this signal. It is known, however, that LPS does not directly condition the activated T cell, therefore, there must be downstream mediators that interact with the activated T cells and uncouple their death pathways. In this study we will determine which factors induced by lipopolysaccharide are essential for rescuing antigen-activated T cells from death. Both in vivo and in vitro experiments will be conducted to determine which cytokines induced by LPS are essential to block death and which death pathways are deregulated in the rescued T cells. A hallmark of a health immune system is the ability to discern self antigen from foreign antigen. All to often a breakdown in tolerance to self antigen occurs which can lead to autoimmune disease. In many cases autoimmunity is associated with inflammatory responses and the effects of inflammation on adaptive immunity are not well understood. The studies described here will lead to a better understanding of the relationship between inflammatory processes and T cell survival. Ultimately these studies may provide a better understanding on how T cells are activated to protect a host from an invading pathogen and how T cells fail self tolerance in the periphery and become autoreactive.